Mirogabalin (DS-5565) is a novel, preferentially selective alpha2delta-1 ligand characterized by high potency and selectivity to the alpha2delta-1 subunit of voltage-sensitive calcium channel complexes in the CNS.
IC50 & Target: alpha2delta-1 Calcium Channel[1]In Vitro: Mirogabalin (DS-5565) is a novel, preferentially selective alpha2delta-1 ligand characterized by high potency and selectivity to the alpha2delta-1 subunit of voltage-sensitive calcium-channel complexes in the central nervous system (CNS). In vitro experiments using membrane preparations from human and rat alpha2delta subunit-expressed cells show that Mirogabalin had a slower dissociation rate from alpha2delta-1 than alpha2delta-2, in particular, alpha2delta-1 compared with Pregabalin. Additionally, Mirogabalin shows potent, sustained analgesic effects in streptozotocin-induced diabetic rats with induces pain, and the superior analgesic effects and wider CNS safety margin relative to Pregabalin are attributed to its selectivity for and slow dissociation from alpha2delta-1 compared with Pregabalin[1]. Mirogabalin (DS-5565) is an alpha2delta-1 ligand being developed for pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. Mirogabalin targets alpha2delta-1, an auxiliary protein associated with voltage-sensitive calcium channel complexes in the central nervous system. This binding reduces calcium influx at nerve terminals, therefore reducing the release of several pain neurotransmitters. The ED50 (on the transformed scale) for Mirogabalin is estimated to be 20.5 mg with a 90% confidence interval (CI) of 10.1-41.7 mg[2].
In Vivo: Additionally, Mirogabalin shows potent, sustained analgesic effects in streptozotocin-induced diabetic rats with induced pain, and the superior analgesic effects and wider central nervous system (CNS) safety margin relative to Pregabalin are attributed to its selectivity for and slow dissociation from alpha2delta-1 compared with Pregabalin[1].